Novel role of human RBCs in vascular tonus: RBCs contribute to adrenergic vasoconstriction via generation of thromboxane A2

Yildirim A., Hapil F. Z., Ozturk N., Yildiz U. A., Cengiz M., Yaras N., ...Daha Fazla

Blood Red Cells & Iron, cilt.2, ss.1-9, 2026 (Hakemli Dergi)

Özet

Red blood cells (RBCs) are increasingly recognized as regulators of vascular tone, capable

of releasing vasodilator substances dependent on local oxygenation status. RBCs can also

induce vasoconstriction, although the identity of the mediator(s) is not clear. We evaluated

whether prostanoids could account for this effect using human RBCs and isolated rat aortic

segments. Freshly prepared RBCs were characterized by flow cytometry and biochemical

assays. Thoracic aortas were procured from anesthetized rats, and segments with intact

endothelium were suspended between wire myographs in Krebs buffer (95% oxygen/5%

carbon dioxide; pH 7.4; 37◦C). Constrictor responses to phenylephrine (Phe) were assessed

in the presence of increasing RBC suspensions (pseudo-hematocrit 10%-55%) and in

combination with adrenergic or prostanoid-active agents. RBCs were found to express the

α1-adrenergic receptors, contain active cyclooxygenase (COX) enzyme, and release

thromboxane A2 (TxA2) after exposure to Phe. In addition, the RBC suspensions were free

of hemoglobin and platelets. In the tissue baths, Phe-mediated vasoconstriction was

augmented by RBCs in a hematocrit-dependent manner. This response was significantly

reduced by indomethacin (nonselective COX inhibitor) and carvedilol (adrenergic receptor

inhibitor). The RBC response was also attenuated by dazoxiben (TxA2 synthesis inhibitor)

and GR32191B (TxA2 receptor antagonist) but not by AL-8810 (prostaglandin F2α receptor

antagonist). Finally, Tx metabolites were elevated in the bath solutions after RBC-enhanced

vasoconstriction. These findings identify RBC-derived TxA2, generated via α1-adrenergic

receptor activation, as a mediator of adrenergic vasoconstriction under oxygenated

conditions. By demonstrating a prostanoid-dependent mechanism, our work provides a

potential mechanism for how RBCs may regulate vasoconstriction in vivo.